(a) Field of the Invention
This invention relates to compounds that are useful in the treatment and prevention of ulcers. More particularly, this invention relates to 2-[(imidazo[1,2-a]pyridinylmethyl)sulfinyl]-1H-benzimidazoles that inhibit gastric acid secretion and which are, therefore, useful in the treatment of peptic ulcers. The compounds of this invention directly inhibit acid secretion by parietal cells of the stomach through inhibition of (H.sup.+ +K.sup.+)-ATPase. For review, see, e.g., J. G. Speeney, "Biochemical Mechanisms of Acid Secretion by Gastric Parietal Cells, " J. Clin. Gastro. 5 (Suppl. 1), 7-15 (1983). In addition, some of the compounds of this invention also exert cytoprotective activity. For review of cytoprotection, see, e.g., U.S. Pat. No. 4,359,465.
(b) Prior Art
Heterocyclylalkylsulfinylbenzimidazoles have been disclosed as gastric acid secretion inhibitors. See U.S. Pat. Nos. 4,472,409, 4,394,509, 4,337,257, 4,327,102, 4,255,431, 4,045,564, and 4,045,563; British Patent No. 2,134,523; German Offenlegungeschrift No. 3,415,971, and Swedish Patent No. 416649. Some heterocyclylalkylsulfinylbenzimidazoles have also been disclosed as cytoprotective agents. See. U.S. Pat. No. 4,359,465. The following structure is illustrative of compounds disclosed in these patents: ##STR1## wherein R' and R" represent hydrogen, alkyl, halogen, trifluoromethyl, cyano, carboxy, hydroxy, acyl, and the like; R'" represents hydrogen, alkyl, acyl, alkoxysulfonyl, and the like; and Het represents heterocyclic groups containing at least one endocyclic (ring) nitrogen. No compound disclosed in these patents includes an imidazo[1,2-a]pyridine ring system, a feature characteristic of the compounds of the present invention.
Heterocyclylalkylsulfinylnaphth[2,3-d]imidazoles have also been disclosed as gastric acid secretion inhibitors. See U.S. Pat. Nos. 4,248,880 and 4,182,766. The compounds disclosed in these patents are related to those illustrated in the above structure, except for having a substituted naphth[2,3-d]imidazole group instead of the benzimidazole group. Similarly, other heterocyclylalkylsulfinylbenzimidazoles having a ring fused to the benzimidazole group have been disclosed as gastric acid secretion inhibitors and cytoprotective agents. See European Patent Application Nos. 130,729 and 127,763. Because of the additional ring fusions of these compounds, as well as for the same reasons stated in the preceding paragraph, the compounds of the present invention are structurally distinguished from prior art compounds cited.
Benzylsulfinylbenzimidazoles have also been disclosed as antiulcer agents. Belgian Patent 903,128. No compounds disclosed in the Belgian patent contain an imidazopyridine ring system, a feature characteristic of the compounds of this invention.